Chronic fructose consumption drives MASH-associated hepato-cardio-renal remodeling through systemic metabolic dysregulation.

Chronic fructose consumption is strongly associated with metabolic dysfunction and metabolic dysfunction-associated steatohepatitis (MASH), yet its contribution to extrahepatic organ remodeling, particularly in the heart and the kidney, remains incompletely characterized. This work characterizes how chronic fructose consumption affects the development of MASH-associated cardiac and renal remodeling and the accompanying metabolic alterations. We established a chronic fructose consumption model in 15-day-old C57BL/6 male mice by adding 33% fructose to the drinking water for 32 weeks. Hepatic miRNA differential-expression analysis identified a miRNA signature associated with chronic fructose exposure, with predicted target pathways enriched for lipid transport and carbohydrate metabolism. Notably, lipid transport was enriched, and non-HDL cholesterol lipoproteins were abundant. Lipid composition in pericardial and perirenal adipose tissue showed a distinct triglyceride signature in the fructose group, which may relate to subclinical cardiorenal alterations that are unresponsive to conventional markers of damage. Chronic fructose consumption was associated with hepatic, cardiac, and renal remodeling accompanied by metabolic alterations. Differential hepatic miRNA expression and adipose tissue triglyceride signatures may represent candidate molecular markers that warrant further validation.